1. Fish in cancer prevention
Dr. Mariette Gerber
Former Senior Scientist INSERM
Expert at the French Food Safety Agency
(ANSES)
June 2018
Dr.Mariette Gerber

2. What nutrients are in fish?
Good quality proteins
As good as meat proteins (without GEG)
Essential fatty acids: Long-Chain omega 3 fatty acids (EPA and DHA)
Because even if a precursor is present in vegetal sources, metabolic transformation in EPA and DHA is at very low rate for EPA and nonexistent for DHA
Because they are an absolute necessity for children’s brain development (DHA)
Vitamin D
Fish is the only natural nutritional source
Increases intestinal absorption of calcium, magnesium, and phosphate
Involved in cell proliferation and differentiation
Improves immune response
June 2018
Dr. Mariette Gerber

3. Epidemiological studies (brief recall)
Methods
Based on dietary and lifestyle questionnaires to inform on all the factors involved in cancer development in order to isolate each specific factor (statistical techniques)
Analytic observationnal studies
Case-control study
Prospective cohort
Meta-analysis: statistical approach to analyse several studies on the same topic in order to increase statistical power
Several studies on colorectal, prostate and breast cancers, insufficient for others
June 2018
Dr .Mariette Gerber

4. Focus on Long-Chain ω 3 fatty acids ?
Based on experimental assays on cell lines showing antiproliferative effect
Mechanistic hypotheses:
Oxidative stress
Change in the plasma membrane
Change in the mitochondrial membrane potential
Epigenetic alterations of the genes involved in apoptosis
Reviewed in “Oncotarget, 2018”, Nutricia Research Centre for specialized nutrition.
Ratio ω3/ω6
Epidemiological studies based on measurement of fish intake in
Questionnaire (fish intake transformed in EPA+ DHA content)
Difficulties: variation in type of fish and fatty acids content
Serum measurement of EPA+DHA (marker of fish intake)
Timing
Dr. Mariette Gerber
June 2018

5. Colorectal cancer and Long-Chain ω 3 fatty acids
Case-control studies (3)
3 risk
Prospective studies (9):
4 risk , 3 no effect, 2risk
Meta-analysis (on 4 studies)
risk : 13%
June 2018
Dr .Mariette Gerber

6. Colorectal cancer and Long-Chain ω 3 fatty acids
Evaluation: « Possible » risk
Limit:difference in protection,heterogeneity
Between studies
Within studies
Sex: risk more important in Men than in Women
Localisation: risk  in patients with distal cancer
Meat replacement?
Recommendation:
Fish to compensate for the decreased meat intake
Colorectal cancer and Long-Chain ω 3 fatty acids
June 2018
Dr .Mariette Gerber

7. Prostate cancer and Long-Chain ω 3 fatty acids
Case-control studies (3)
2 risk of cancer, 1 no effect
Prospective studies (7):
2 risk, 2 no effect, 3 risk
Meta-analysis (on 2 studies)
 risk for advanced tumors
Evaluation
Too much heterogeneity
Use of markers combined with fish oil intake
No recommendation
June 2018
Dr .Mariette Gerber

8. Breast cancer and Long-Chain ω 3 fatty acids
Case-control studies (5)
5 risk: 4 in Asia, 1 in Southern France
Prospective studies (7):
4 no effect
3 risk: 2 from Asia, 1 USA (current use of fish oil)
Meta-analysis (17 cohorts)
Analysis based on questionnaires (8) or plasma measurements (11): both show risk 15%
Analysis by subgroups higher  risk for
F Mnp+
Women from Asia
June 2018
Dr. Mariette Gerber

9. Breast cancer and Long-Chain ω 3 fatty acids
Evaluation
Heterogeneity in prospective studies suggests a limited certitude of risk :”possible to probable”
But why Asian women and Women Mnp+ appeared more protected?
Mnp+ BC: Food/diet, lifestyle is an important factor
Asian women: quantity of fish and/or to the whole diet
June 2018
Dr .Mariette Gerber

10. What can be concluded?
Although supported by experimental studies, biological plausibility, evidence of a relationship between 3 fatty acids and cancers is limited
Was the focus on 3 fatty acids misleading? High errors possible (variable content)
Although 3 fatty acids are markers of fish, can they translate all the benefits of fish?
Why not look at the effect of fish as a food and to dietary pattern?
June 2018
Dr .Mariette Gerber

11. Fish and cancers Breast cancer 7 prospective studies
Colorectal cancer (China)
1 case control study risk 53%
WCRF(2007): limited evidence of risk through fish consumption
Breast cancer 7 prospective studies
2 risk: Norway 30% (poached fish) 5 times/week Japan 50% 5 times/week
3 NS: all from USA
2 risk: both from Denmark
Again the same discrepancies and variability: limited evidence of risk
However obvious differences by countries:
Type of fish, quantity, cooking, the whole diet? Which dietary pattern?
June 2018
Dr .Mariette Gerber

12. Usual dietary patterns
« Western » related to  risk of cancers
Constant:
meat and processed meat, potatoes, butter, refined grains, high fat dairy products
Depending upon the studies and populations
Eggs, cream, pizzas/pies, mayonnaise, French fries, coffee, alcohol
« Healthy/Prudent » related to  risk of cancers
Constant
fruit, vegetables, legumes, fish, sea-food, whole grains
Poultry, vegetable oils, low fat dairy products, fruit juices, moderate intake of wine.
« Mediterranean » 
Healthy/Prudent + olive oil, herbs
June 2018
Dr .Mariette Gerber

13. Dietary patterns and Breast cancer Post-Menopausal women
Alcohol / Healthy/
Western Mediterranean
p trend
E3N (Cottet et al, 2009)
June 2018
Dr .Mariette Gerber

14. Mediterranean diet and cancers
Hormono-dependant cancers
Probable risk of breast cancer with Mediterranean diet, (fewer studies for prostate)
Colorectal cancer
Possible risk
Environmentally related cancers
limited evidence of risk reduction for head and neck, lung, gastric, bladder cancers
June 2018
Dr .Mariette Gerber

15. Mediterranean diet: a lifestyle
Physical activity
Meals are structured around dishes
Meals are shared with parents, friends, colleagues
No snacking
To be added:
Quality of food and of environment
June 2018
Dr .Mariette Gerber

16. Fish contamination Possible contaminants: WHO/FAO report (2010):
Methyl mercure (MeHG),
Mainly present in large fish, predators
Dioxins and polychlorinated biphenyls (PCB),
Accumulation in fat, mainly present in blue fish (endocrine disruptors)
WHO/FAO report (2010):
The health risks of not consuming fish outweigh the potential risks from MeHG and other contaminants
More studies on MeHG than on PCBs supporting this conclusion
June 2018
Dr .Mariette Gerber

17. Fish consumption and mortality EPIC study (2015)
Prospective study > 500,000 participants, 10 European countries
No significant risk reduction of fish consumption on total and cancer mortality, but a significant trend for a U shaped response for both
Especially observed from Danish population sample
What does that mean?
June 2018
Dr .Mariette Gerber

18. Risk of mortality and fish consumption (Denmark EPIC study)
Legend: g/day
Q1: 2 # <1/month
Q2: 11 # 2/month
Q3: 21 # 1/week (Ref)
Q4: 34 # 3/week
Q5: 76 # 5/week 
1.25
1.24
1.14
1.07 1 Q1 Q2 Q3 Q4 Q5
June 2018
Dr .Mariette Gerber

19. Summary
Because of inherent difficulties of epidemiological methods, risk reduction of cancer cannot be ascertained, but possible to probable for colorectal and breast cancers
Recommendations in European countries:
Eat fish 2 to 3 times a week (fish portion 100 to 150g), with 1 to 2 times fatty fish.
A diet including fish together with other beneficial foods, such as the Mediterranean diet, is highly recommended to reduce cancer
To keep this advantage all of us have to fight against ocean pollution, and for your organization it is a “must”
June 2018
Dr .Mariette Gerber

20. Thank you for your attention